Noradrenergic ensemble-based modulation of cognition over multiple timescales.

Cognition fluctuates over relatively faster and slower timescales. This is enabled by dynamic interactions among cortical neurons over similarly diverse temporal and spatial scales. Fast and slow cognitive processes, such as reorienting to surprising stimuli or using experience to develop a behavioral strategy, are also sensitive to neuromodulation by the diffusely-projecting brainstem noradrenergic nucleus, Locus Coeruleus. However, while a dynamic, multi-scale cortical ensemble code influences cognition over multiple timescales, it is unknown to what extent LC neuronal activity operates in this regime. An ensemble code within the LC may permit an interface with cortical ensembles allowing noradrenergic modulation of fast and slow cognitive processes. Alternatively, given that LC neurons are thought to spike synchronously, there may be a mismatch between LC and cortical neuronal codes that constrains how the noradrenergic system can influence cognition. We review new evidence that clearly demonstrates cell type-specific ensemble activity within LC occurring over a range of behaviorally-relevant timescales. We also review recent studies demonstrating that sub-sets of LC neurons modulate specific forebrain targets to control behavior. A critical target for future research is to study the temporal dynamics of projection-specific LC ensembles, their interactions with cortical networks, and the relevance of multi-scale coerular-cortical dynamics to behaviors over various timescales.